Skip to main content

Advertisement

SpringerLink
Log in

Clinical Description of the Lynch Syndrome [Hereditary Nonpolyposis Colorectal Cancer (HNPCC)]

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

The Lynch syndrome [Hereditary Nonpolyposis Colorectal Cancer (HNPCC)] is a dominantly inherited syndrome characterized by the development of a variety of cancers including cancer of colorectum, endometrium, and less frequently, cancer of the small bowel, stomach, urinary tract, ovaries, and brain. The syndrome is due to a mutation in one of the DNA-mismatch repair (MMR) genes. The main features of the syndrome are an early age of onset and the occurrence of multiple tumors. Knowledge of the specific features of the syndrome is crucial for the identification of the Lynch syndrome. In previous years, the Amsterdam criteria were used for recognition of the syndrome. Since we know that the Lynch syndrome is caused by an MMR defect and that the hallmark of the syndrome is microsatellite instability (MSI), more attention should be given to the so-called Bethesda guidelines. These guidelines describe practically all clinical conditions in which there is suspicion of the Lynch syndrome and in which a search for MSI is indicated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. HT Lynch CA. la Particlede (2003) ArticleTitleHereditary colorectal cancer N Engl J Med 348 919–32 Occurrence Handle10.1056/NEJMra012242 Occurrence Handle12621137

    Article  PubMed  Google Scholar 

  2. P Peltomaki HF. Vasen (1997) ArticleTitleMutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer Gastroenterology 113 1146–58 Occurrence Handle9322509

    PubMed  Google Scholar 

  3. LA Aaltonen R Salovaara P Kristo et al. (1998) ArticleTitleIncidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease N Engl J Med 338 1481–7 Occurrence Handle10.1056/NEJM199805213382101 Occurrence Handle9593786

    Article  PubMed  Google Scholar 

  4. DC Desai JC Lockman RB Chadwick et al. (2000) ArticleTitleRecurrent germline mutation in MSH2 arises frequently de novo J Med Genet 37 646–52 Occurrence Handle10.1136/jmg.37.9.646 Occurrence Handle10978353

    Article  PubMed  Google Scholar 

  5. C Kraus S Kastl K Gunther et al. (1999) ArticleTitleA proven de novo germline mutation in HNPCC J Med Genet 36 919–21 Occurrence Handle10594000

    PubMed  Google Scholar 

  6. J Wijnen W De Leeuw H Vasen et al. (1999) ArticleTitleFamilial endometrial cancer in female carriers of MSH6 germline mutations Nat Genet 23 142–4 Occurrence Handle10.1038/13773 Occurrence Handle10508506

    Article  PubMed  Google Scholar 

  7. Warthin AS. Heredity with reference to carcinoma. Arch Int Med: 12: 546–55.

  8. HT Lynch AJ. Krush (1971) ArticleTitleCancer family “G” revisited: 1895–1970 Cancer 27 1505–11 Occurrence Handle5088221

    PubMed  Google Scholar 

  9. JG Park YJ Park JT Wijnen HF. Vasen (1999) ArticleTitleGene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing Int J Cancer 82 516–9 Occurrence Handle10.1002/(SICI)1097-0215(19990812)82:4<516::AID-IJC8>3.0.CO;2-U Occurrence Handle10404064

    Article  PubMed  Google Scholar 

  10. P Watson HT. Lynch (1993) ArticleTitleExtracolonic cancer in hereditary nonpolyposis colorectal cancer Cancer 71 677–85 Occurrence Handle8431847

    PubMed  Google Scholar 

  11. HF Vasen JT Wijnen FH Menko et al. (1996) ArticleTitleCancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis Gastroenterology 110 1020–7 Occurrence Handle8612988

    PubMed  Google Scholar 

  12. HF Vasen EA Sanders BG Taal et al. (1996) ArticleTitleThe risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC) Int J Cancer 65 422–5 Occurrence Handle10.1002/(SICI)1097-0215(19960208)65:4<422::AID-IJC4>3.0.CO;2-Z Occurrence Handle8621220

    Article  PubMed  Google Scholar 

  13. RH Sijmons LA Kiemeney JA Witjes HF. Vasen (1998) ArticleTitleUrinary tract cancer and hereditary nonpolyposis colorectal cancer: risks and screening options J Urol 60 466–70 Occurrence Handle10.1097/00005392-199808000-00048

    Article  Google Scholar 

  14. M Aarnio R Sankila E Pukkala et al. (1999) ArticleTitleCancer risk in mutation carriers of DNA-mismatch-repair genes Int J Cancer 81 214–8 Occurrence Handle10.1002/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.0.CO;2-L Occurrence Handle10188721

    Article  PubMed  Google Scholar 

  15. RJ Scott M McPhillips CJ Meldrum et al. (2001) ArticleTitleHereditary nonpolyposis colorectal cancer in 95 families: Differences and similarities between mutation-positive and mutation-negative kindreds Am J Hum Genet 68 118–27 Occurrence Handle10.1086/316942 Occurrence Handle11112663

    Article  PubMed  Google Scholar 

  16. HF Vasen H Morreau JW. Nortier (2001) ArticleTitleIs breast cancer part of the tumor spectrum of hereditary nonpolyposis colorectal cancer? Am J Hum Genet 68 1533–5 Occurrence Handle10.1086/320610 Occurrence Handle11359214

    Article  PubMed  Google Scholar 

  17. C Soravia KH der Particlevan MA Brundler et al. (2003) ArticleTitleProstate cancer is part of the hereditary non-polyposis colorectal cancer (HNPCC) tumor spectrum Am J Med Genet 121 159–62 Occurrence Handle10.1002/ajmg.a.20106

    Article  Google Scholar 

  18. M Aarnio JP Mecklin LA Aaltonen et al. (1995) ArticleTitleLife-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome Int J Cancer 64 430–3 Occurrence Handle8550246

    PubMed  Google Scholar 

  19. HF Vasen A Stormorken FH Menko et al. (2001) ArticleTitleMSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: A study of hereditary nonpolyposis colorectal cancer families J Clin Oncol 19 4074–80 Occurrence Handle11600610

    PubMed  Google Scholar 

  20. MG Dunlop SM Farrington AD Carothers et al. (1997) ArticleTitleCancer risk associated with germline DNA mismatch repair gene mutations Hum Mol Genet 6 105–10 Occurrence Handle10.1093/hmg/6.1.105 Occurrence Handle9002677

    Article  PubMed  Google Scholar 

  21. YM Hendriks A Wagner H Morreau et al. (2004) ArticleTitleCancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: Impact on counseling and surveillance Gastroenterology 127 17–25 Occurrence Handle10.1053/j.gastro.2004.03.068 Occurrence Handle15236168

    Article  PubMed  Google Scholar 

  22. J Carayol M Khlat J Maccario C. Bonaiti-Pellie (2002) ArticleTitleHereditary non-polyposis colorectal cancer: Current risks of colorectal cancer largely overestimated J Med Genet 39 335–9 Occurrence Handle10.1136/jmg.39.5.335 Occurrence Handle12011152

    Article  PubMed  Google Scholar 

  23. P Watson HF Vasen JP Mecklin et al. (1994) ArticleTitleThe risk of endometrial cancer in hereditary nonpolyposis colorectal cancer Am J Med 96 516–20 Occurrence Handle10.1016/0002-9343(94)90091-4 Occurrence Handle8017449

    Article  PubMed  Google Scholar 

  24. KM Lin M Shashidharan CA Ternent et al. (1998) ArticleTitleColorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population Dis Colon Rectum 41 428–33 Occurrence Handle9559626

    PubMed  Google Scholar 

  25. FH Menko GJ te Meerman JR. Sampson (1993) ArticleTitleVariable age of onset in hereditary nonpolyposis colorectal cancer: Clinical implications Gastroenterology 104 946–7 Occurrence Handle8440450

    PubMed  Google Scholar 

  26. DW Voskuil HF Vasen E Kampman P. ’t Veer Particlevan (1997) ArticleTitleColorectal cancer risk in HNPCC families: Development during lifetime and in successive generations National Collaborative Group on HNPCC. Int J Cancer 72 205–9

    Google Scholar 

  27. YY Tsai GM Petersen SV Booker et al. (1997) ArticleTitleEvidence against genetic anticipation in familial colorectal cancer Genet Epidemiol 14 435–46 Occurrence Handle10.1002/(SICI)1098-2272(1997)14:4<435::AID-GEPI8>3.0.CO;2-1 Occurrence Handle9271715

    Article  PubMed  Google Scholar 

  28. AE De Jong M Van Puijenbroek Y Hendriks et al. (2004) ArticleTitleMicrosatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer Clin Cancer Res 10 972–80 Occurrence Handle14871975

    PubMed  Google Scholar 

  29. WH VostotNederveen Cappel Particlede E Buskens P Duijvendijk Particlevan et al. (2003) ArticleTitleDecision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect Gut 52 1752–5 Occurrence Handle10.1136/gut.52.12.1752 Occurrence Handle14633956

    Article  PubMed  Google Scholar 

  30. AE De Jong H Morreau M Van Puijenbroek et al. (2004) ArticleTitleThe role of mismatch repair gene defects in the development of adenomas in patients with HNPCC Gastroenterology 126 42–8 Occurrence Handle10.1053/j.gastro.2003.10.043 Occurrence Handle14699485

    Article  PubMed  Google Scholar 

  31. JR Jass SM Stewart J Stewart MR. Lane (1994) ArticleTitleHereditary non-polyposis colorectal cancer–morphologies, genes and mutations Mutat Res 310 125–33 Occurrence Handle7523876

    PubMed  Google Scholar 

  32. HF Vasen FM Nagengast PM. Khan (1995) ArticleTitleInterval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome) Lancet 345 1183–4 Occurrence Handle10.1016/S0140-6736(95)91016-6 Occurrence Handle7723574

    Article  PubMed  Google Scholar 

  33. R Sankila LA Aaltonen HJ Jarvinen JP. Mecklin (1996) ArticleTitleBetter survival rates in patients with MLH1-associated hereditary colorectal cancer Gastroenterology 110 682–7 Occurrence Handle10.1053/gast.1996.v110.pm8608876 Occurrence Handle8608876

    Article  PubMed  Google Scholar 

  34. JR Jass MD Walsh M Barker et al. (2002) ArticleTitleDistinction between familial and sporadic forms of colorectal cancer showing DNA microsatellite instability Eur J Cancer 38 858–66 Occurrence Handle10.1016/S0959-8049(02)00041-2 Occurrence Handle11978509

    Article  PubMed  Google Scholar 

  35. JM Carethers DP Chauhan D Fink et al. (1999) ArticleTitleMismatch repair proficiency and in vitro response to 5-fluorouracil Gastroenterology 117 123–31 Occurrence Handle10381918

    PubMed  Google Scholar 

  36. JM Carethers EJ Smith CA Behling et al. (2004) ArticleTitleUse of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer Gastroenterology 126 394–401 Occurrence Handle10.1053/j.gastro.2003.12.023 Occurrence Handle14762775

    Article  PubMed  Google Scholar 

  37. WH VostotNederveen Cappel Particlede HJ Meulenbeld JH Kleibeuker et al. (2004) ArticleTitleSurvival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer Int J Cancer 109 468–71 Occurrence Handle10.1002/ijc.11712 Occurrence Handle14961589

    Article  PubMed  Google Scholar 

  38. CM Ribic DJ Sargent MJ Moore et al. (2003) ArticleTitleTumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer N Engl J Med 349 247–57 Occurrence Handle10.1056/NEJMoa022289 Occurrence Handle12867608

    Article  PubMed  Google Scholar 

  39. ˙E Boks AP Trujillo AC Voogd et al. (2002) ArticleTitleSurvival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer Int J Cancer 102 198–200 Occurrence Handle10.1002/ijc.10667 Occurrence Handle12385019

    Article  PubMed  Google Scholar 

  40. WJ Leeuw Particlede J Dierssen HF Vasen et al. (2000) ArticleTitlePrediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patients J Pathol 192 328–35 Occurrence Handle10.1002/1096-9896(2000)9999:9999<::AID-PATH701>3.0.CO;2-2 Occurrence Handle11054716

    Article  PubMed  Google Scholar 

  41. P Watson R Butzow HT Lynch et al. (2001) ArticleTitleThe clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer Gynecol Oncol 82 223–8 Occurrence Handle10.1006/gyno.2001.6279 Occurrence Handle11531271

    Article  PubMed  Google Scholar 

  42. M Aarnio R Salovaara LA Aaltonen et al. (1997) ArticleTitleFeatures of gastric cancer in hereditary non-polyposis colorectal cancer syndrome Int J Cancer 74 551–5 Occurrence Handle10.1002/(SICI)1097-0215(19971021)74:5<551::AID-IJC13>3.0.CO;2-9 Occurrence Handle9355980

    Article  PubMed  Google Scholar 

  43. MA Rodriguez-Bigas HF Vasen HT Lynch et al. (1998) ArticleTitleCharacteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma International Collaborative Group on HNPCC. Cancer 83 240–4

    Google Scholar 

  44. SR Hamilton B Liu RE Parsons et al. (1995) ArticleTitleThe molecular basis of Turcot’s syndrome N Engl J Med 332 839–47 Occurrence Handle10.1056/NEJM199503303321302 Occurrence Handle7661930

    Article  PubMed  Google Scholar 

  45. HF Vasen JP Mecklin PM Khan HT. Lynch (1991) ArticleTitleThe International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) Dis Colon Rectum 34 424–5 Occurrence Handle10.1007/BF02053699 Occurrence Handle2022152

    Article  PubMed  Google Scholar 

  46. HF Vasen P Watson JP Mecklin HT. Lynch (1999) ArticleTitleNew clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC Gastroenterology 116 1453–6 Occurrence Handle10348829

    PubMed  Google Scholar 

  47. BV Bapat L Madlensky LK Temple et al. (1999) ArticleTitleFamily history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer Hum Genet 104 167–76 Occurrence Handle10.1007/s004390050931 Occurrence Handle10190329

    Article  PubMed  Google Scholar 

  48. S Fujita Y Moriya K Sugihara et al. (1996) ArticleTitlePrognosis of hereditary nonpolyposis colorectal cancer (HNPCC) and the role of Japanese criteria for HNPCC Jpn J Clin Oncol 26 351–5 Occurrence Handle8895676

    PubMed  Google Scholar 

  49. MA Rodriguez-Bigas CR Boland SR Hamilton et al. (1997) ArticleTitleA national cancer institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines J Natl Cancer Inst 89 1758–62 Occurrence Handle10.1093/jnci/89.23.1758 Occurrence Handle9392616

    Article  PubMed  Google Scholar 

  50. JG Park HF Vasen KJ Park et al. (1999) ArticleTitleSuspected hereditary nonpolyposis colorectal cancer: international Collaborative Group on hereditary non-polyposis colorectal cancer (ICG-HNPCC) criteria and results of genetic diagnosis Dis Colon Rectum 42 710–5 Occurrence Handle10378593

    PubMed  Google Scholar 

  51. CR Boland SN Thibodeau SR Hamilton et al. (1998) ArticleTitleA national cancer institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer Cancer Res 58 5248–57 Occurrence Handle9823339

    PubMed  Google Scholar 

  52. A Umar CR Boland JP Terdiman et al. (2004) ArticleTitleRevised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability J Natl Cancer Inst 96 261–8 Occurrence Handle14970275

    PubMed  Google Scholar 

  53. JP Mecklin HJ Jarvinen P. Peltokallio (1986) ArticleTitleCancer family syndrome. Genetic analysis of 22 Finnish kindreds Gastroenterology 90 328–33 Occurrence Handle3940911

    PubMed  Google Scholar 

  54. dL Ponz R Sassatelli C Sacchetti et al. (1989) ArticleTitleFamilial aggregation of tumors in the three-year experience of a population-based colorectal cancer registry Cancer Res 49 4344–8 Occurrence Handle2743323

    PubMed  Google Scholar 

  55. HF Vasen FC Hartog Jager FH Menko FM. Nagengast (1989) ArticleTitleScreening for hereditary non-polyposis colorectal cancer: A study of 22 kindreds in the Netherlands Am J Med 86 278–81 Occurrence Handle10.1016/0002-9343(89)90296-9 Occurrence Handle2919609

    Article  PubMed  Google Scholar 

  56. AS. Warthin (2004) ArticleTitleHeredity of carcinoma in man Ann Int med 4 681–96

    Google Scholar 

  57. HT Lynch JF. Lynch (1994) ArticleTitle25 years of HNPCC Anticancer Res 14 1617–24 Occurrence Handle7979196

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Leiden University Medical Centre, Leiden, The Netherlands

    H. F. A. Vasen

  2. Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands

    H. F. A. Vasen

  3. The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden University Medical Centre (Poortgebouw), Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands

    H. F. A. Vasen

Authors
  1. H. F. A. Vasen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. F. A. Vasen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vasen, H.F.A. Clinical Description of the Lynch Syndrome [Hereditary Nonpolyposis Colorectal Cancer (HNPCC)]. Familial Cancer 4, 219–225 (2005). https://doi.org/10.1007/s10689-004-3906-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-004-3906-5

Keywords

Search

Navigation